INTESTINAL MUCOSAL GROWTH IN HEALTH & SURGICAL DISEASE

健康的肠粘膜生长

• 批准号: 6635275
• 负责人: Jian-Ying Wang
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635275
• 关键词: cell growth regulation; cell proliferation; gene expression; growth inhibitors; in situ hybridization; intestinal mucosa; laboratory rat; oncoprotein p21; p53 gene /protein; polyamines; tissue /cell culture; transfection

The inhibition of gastrointestinal mucosal growth occurs commonly in critical illness including a variety of surgical conditions. Data from the Investigator's laboratory and others indicate that the supply of polyamines to the dividing cells is an important step in the regulation of normal intestinal mucosal growth and that decreasing cellular polyamines inhibits cell renewal. The goal of this project is to elucidate the fundamental mechanisms by which the intestinal mucosal renewal process is impaired following polyamine depletion. The hypothesis is that inhibition of polyamine synthesis suppresses intestinal mucosal growth by altering expression of the p53 gene. Four specific aims are proposed: 1) to identify the relationship between expression of the p53 gene and growth inhibition in small intestinal mucosa in vivo, 2) to determine the role of cellular polyamines in p53 gene expression in intestinal crypt cells in vitro. The Investigators will first define the level where the effect of polyamines on p53 gene expression occurs and then concentrate on understanding the mechanism by which polyamines modulate post-transcription of the p53 gene, 3) to determine the role of increased p53 gene expression in growth inhibition following polyamine depletion. The Investigators will determine whether decreasing p53 levels by antisense oligonucleotides or increasing p53 levels by transfecting a conditional p53 expression vector alters intestinal epithelial cell growth in the presence or absence of polyamines, 4) to identify the basic mechanism by which p53 results in the growth inhibition following polyamine depletion. The Investigators will elucidate the role of p21cip1/waf1 in p53-mediated inhibition of intestinal epithelial cell proliferation in polyamine-deficient cells. The Investigators propose that these studies will enhance understanding of the biology of intestinal mucosal growth and have broader implications for the pathophysiology of mucosal growth inhibition in critical illness.

胃肠道粘膜生长的抑制通常发生在 包括各种外科手术在内的危重病患者。 的数据 研究人员的实验室和其他机构指出， 分裂细胞是调节正常肠道功能的重要步骤， 粘膜生长和减少细胞多胺抑制细胞更新。 这个项目的目标是阐明基本的机制， 肠粘膜更新过程在多胺后受损 耗尽 假设是多胺合成的抑制抑制了 通过改变p53基因的表达来抑制肠粘膜生长。 四 具体目标是：1）确定表达之间的关系 p53基因和生长抑制在体内小肠粘膜，2） 确定细胞多胺在肠上皮细胞p53基因表达中的作用 体外培养的隐窝细胞。 调查人员将首先确定 多胺对p53基因表达影响发生，然后集中于 了解多胺调节转录后的机制， p53基因，3）以确定增加的p53基因表达的作用， 多胺耗尽后的生长抑制。 调查人员将 确定是否通过反义寡核苷酸或 通过转染条件性p53表达载体增加p53水平 改变肠上皮细胞的生长，在存在或不存在 多胺，4）以确定p53导致的基本机制， 多胺耗尽后的生长抑制。 调查人员将 阐明p21 cip 1/waf 1在p53介导的肠上皮细胞增殖抑制中的作用 多胺缺陷细胞中的上皮细胞增殖。 调查人员 建议这些研究将提高对生物学的理解 肠粘膜生长，并具有更广泛的病理生理学意义 粘膜生长抑制的症状